Glucosidase II (GluII) is a heterodimeric enzyme localized in the endoplasmic reticulum (ER), essential for the sequential trimming of glucose residues during N-linked glycosylation. This critical function facilitates glycoprotein folding via the calnexin/calreticulin chaperone system, maintaining ER homeostasis. Dysregulation or inhibition of GluII has been implicated in various pathological processes, including cancer, viral infections, and glycoprotein misfolding disorders. This review summarizes the current knowledge of GluII’s structure and function, highlights a wide range of natural and synthetic GluII inhibitors—including iminosugar derivatives (e.g., deoxynojirimycin (DNJ), castanospermine (CAST)), non-iminosugar compounds (e.g., bromoconduritol, catechins), and mechanism-based cyclophellitol analogues—and evaluates their biological effects and therapeutic potential. The cellular impact of GluII inhibition is explored in the context of ER stress, unfolded protein response (UPR), tumor cell apoptosis, and viral replication. Key challenges in developing selective GluII inhibitors are discussed, with a focus on strategies to minimize off-target effects, including prodrug design, allosteric modulation, and emerging genetic approaches such as microRNA (miRNA)-mediated downregulation of GluII subunits. Taken together, these insights underscore the therapeutic relevance of GluII as a druggable target and pave the way for the rational design of next-generation inhibitors in oncology, infectious diseases, and metabolic disorders.

Chronic myelogenous leukemia (CML) is a serious threat to human health, while drugs for CML are limited. Herbal medicines with structural diversity, low toxicity and low drug resistance are always the most important source for drug discoveries. Gynura divaricata (L.) DC. is a well-known herbal medicine whose non-alkaline ingredients (GD-NAIs) were isolated. The GD-NAIs demonstrated potential anti-CML activity in our preliminary screening tests. However, the chemical components and underlying mechanism are still unknown. In this study, GD-NAIs were tentatively characterized using UHPLC-HRMS combined with molecular networking, which were composed of 75 sesquiterpenoids. Then, the anti-CML activities of GD-NAIs were evaluated and demonstrated significant suppression of proliferation and promotion of apoptosis in K562 cells. Furthermore, the mechanism of GD-NAIs against CML were elucidated using network pharmacology combined with RNA sequencing. Four sesquiterpenoids would be the main active ingredients of GD-NAIs against CML, which could regulate PD-L1 expression and the PD-1 checkpoint pathway in cancer, PI3K/AKT, JAK/STAT, TGF-β, estrogen, Notch and Wnt signaling pathways. In conclusion, our study reveals the composition of GD-NAIs, confirms its anti-CML activity and elucidates their underlying mechanism, which is a potential countermeasure for the treatment of CML.

Residential radon is a leading environmental cause of lung cancer, but circulating biomarkers linking home exposure to pathogenic biology are not well defined. We conducted an exposure-contrast study in Hang Dong District, Chiang Mai, measuring indoor radon in 48 homes and enrolling adults from <50 Bq/m³ (low) and ≥100 Bq/m³ (high) households for serum profiling. Mean indoor radon was 61.8 ± 18.4 Bq/m³ (range 34–126), with 6.2% of homes ≥100 Bq/m³. Small RNA sequencing identified 55 differentially expressed miRNAs (12 up, 43 down) in high-radon serum. Notably, miR-200b-3p, miR-200c-3p, and miR-194-5p were increased, while miR-3913-5p, miR-584-5p, miR-30a-3p, miR-22-3p, and miR-125a-5p were decreased. Target enrichment (KEGG/GO) implicated PI3K–Akt and MAPK hubs with Ras/Wnt/VEGF alongside focal adhesion/ECM–receptor/actin–cytoskeleton and immune-regulatory modules. Untargeted LC–MS metabolomics showed exposure-aligned shifts: higher PUFAs and oxylipins (e.g., AA, EPA; 9-HEPE, 8-HETE, 5,12-DiHETE), elevated acyl-carnitines (β-oxidation), and increased inosine/hypoxanthine, consistent with lipid/steroid remodeling, mitochondrial fuel reprogramming, oxidative stress, and nucleotide turnover. Integrated interpretation supports DDR/ATM → PI3K/Akt–MAPK activation with EMT/adhesion remodeling, angiogenic signaling, and immune modulation—linking residential radon to lung cancer mechanisms. Given the small sample size (n = 10), these findings should be interpreted as preliminary and hypothesis-generating, warranting validation in larger cohorts. Nevertheless, findings support household testing, remediation at ≥100 Bq/m³, and integrated exposure studies considering PM2.5 co-exposures.

Background: Stress is a risk factor for metabolic syndrome (MetS). High and low sensory stimulation can trigger high stress, but no research exists on the relationship between sensory processing patterns and stress among people with MetS. Objective: This study examined the association between sensory processing patterns and stress. Materials and methods: A total of 117 people with MetS in the Nam Phrea subdistrict, Hang-Dong District, Chiang-Mai Province, Thailand, aged 35-85, completed the Thai Sensory Patterns Assessment-Adult Version (TSPA) and the Thai Stress Test (TST-24). Demographic and metabolic variable information was gathered. Descriptive statistics were used to summarize the demographic characteristics and stress. Spearman’s correlation and regression analysis examined the associations between the sensory processing patterns in each sensory modality and stress scores. Results: A total stress score was significantly correlated with preferences in visual and auditory senses, as well as with arousal levels in visual and smell-taste senses (r =-0.397, -0.199, -0.358, 0.268, and p<0.05). Regression analysis revealed that stress can be predicted by preferences and arousal levels in visual and smell-taste senses (R2 =0.156, 0.039, 0.174, and 0.050, respectively; p<0.05). Conclusion: The results suggest that sensory processing patterns might associated with stress, which is a predictor of MetS. Health professionals can utilize acquired knowledge to implement sensory-based interventions for individuals with MetS to address their stress issues.